Historically, people of almost every culture have used chemical agents
to induce sleep, relieve stress, and allay anxiety. While alcohol is
one
of the oldest and most universal agents used for these purposes,
hundreds of substances have been developed that produce central
nervous
system depression. These drugs have been referred to as downers,
sedatives, hypnotics, minor tranquilizers, anxiolytics, and
anti-anxiety
medications. Unlike most other classes of drugs of abuse, depressants
are rarely produced in clandestine laboratories. Generally, legitimate
pharmaceutical products are diverted to the illicit market. A notable
exception to this is a relatively recent drug of abuse, gamma
hydroxybutyric acid (GHB).

Choral hydrate
and
paraldehyde are two of the oldest pharmaceutical depressants still in
use today. Other depressants, including gluthethimide, methaqualone,
and
meprobamate have been important players in the milieu of depressant
use
and abuse. However, two major groups of depressants have dominated the
licit and illicit market for nearly a century, first barbiturates and
now benzodiazepines.

Barbiturates
were
very popular in the first half of the 20th century. In moderate
amounts,
these drugs produce a state of intoxication that is remarkably similar
to alcohol intoxication. Symptoms include slurred speech, loss of
motor
coordination, and impaired judgment. Depending on the dose, frequency,
and duration of use, one can rapidly develop tolerance, physical
dependence, and psychological dependence to barbiturates. With the
development of tolerance, the margin of safety between the effective
dose and the lethal dose becomes very narrow. That is, in order to
obtain the same level of intoxication, the tolerant abuser may raise
his
or her dose to a level that may result in coma or death. Although many
individuals have taken barbiturates therapeutically without harm,
concern about the addiction potential of barbiturates and the
ever-increasing number of fatalities associated with them led to the
development of alternative medications. Today, less than 10 percent of
all depressant prescriptions in the United States are for
barbiturates.

Benzodiazepines
were first marketed in the 1960s. Touted as much safer depressants
with
far less addiction potential than barbiturates, today these drugs
account for about one out of every five prescriptions for controlled
substances. Although benzodiazepines produce significantly less
respiratory depression than barbiturates, it is now recognized that
benzodiazepines share many of the undesirable side effects of the
barbiturates. A number of toxic central nervous system effects are
seen
with chronic high-dose benzodiazepine therapy, including headaches,
irritability, confusion, memory impairment and depression. The risk of
developing over-sedation, dizziness, and confusion increases
substantially with higher doses of benzodiazepines. Prolonged use can
lead to physical dependence even at doses recommended for medical
treatment. Unlike barbiturates, large doses of benzodiazepines are
rarely fatal unless combined with other drugs or alcohol. Although
primary abuse of benzodiazepines is well documented, abuse of these
drugs usually occurs as part of a pattern of multiple drug abuse. For
example, heroin or cocaine abusers will use benzodiazepines and other
depressants to augment their "high" or alter the side effects
associated
with over-stimulation or narcotic withdrawal.

In recent years,
GHB has emerged as a significant drug of abuse throughout the United
States. Abusers of this drug fall into three major groups: (1) users
who
take GHB for its MDMA-like hallucinogenic effects or as an intoxicant
or
euphoriant; (2) bodybuilders who abuse GHB for its alleged utility as
an
anabolic agent or as a sleep aid; and (3) individuals who use GHB as a
weapon for sexual assault. These categories are not mutually exclusive
and an abuser may use the drug illicitly to produce several effects.
GHB
is frequently taken with alcohol or other drugs that heightens its
effects and is often found at bars, nightclubs, rave parties, and
gyms.
Teenagers and young adults who frequent these establishments are the
primary users. Like flunitrazepam, benzodiazepine is often referred to
as a "date-rape" drug, and GHB involvement in rape cases is likely to
be
unreported or unsubstantiated. GHB is quickly eliminated from the body
making detection in body fluids unlikely; and its fast onset of
depressant effects may render the victim with little memory of the
details of the attack.

There are marked
similarities among the withdrawal symptoms seen with most drugs
classified as depressants. In the mildest form, the withdrawal
syndrome
may produce insomnia and anxiety, usually the same symptoms that
initiated the drug use. With a greater level of dependence, tremors
and
weakness are also present, and in its most severe form, the withdrawal
syndrome can cause seizures and delirium. Unlike the withdrawal
syndrome
seen with most other drugs of abuse, withdrawal from depressants can
be
life threatening.